GOALS - The process of conversion of a normal cell to a malignant cell is, in almost all instances, a multistep process which involves the subversion or alteration of normal cellular and molecular processes that regulate cell growth and differentiation to abnormal process which play a direct role in loss of growth control and/or differentiation. Recent advances in molecular biology have led to the identification and characterization of several of the important components of normal growth and differentiation pathways in many different cell types representing all three germ lines. i.e. tissues from endoderm, mesoderm and ectoderm. In several instances these processes are unique to a given cell or tissue type while in others they appear to be more generic and similar if not identical across multiple cell and tissue types. Recent data indicate that one of the important processes which shares many similarities between different cell types is the process of signal transduction beginning with activation of cell surface receptors by cognate ligands, to the transfer of the surface signal to cytoplasmic signaling molecules to the ultimate transduction of the signal into the nucleus with the resultant transcription of specific genes leading to cell growth or differentiation. The overall goal of this Program Project is to study component parts of this process in a series of relevant mammalian cell systems with the hope of gaining greater insights into both the normal and abnormal function of the molecular events which occur. Interaction among and between the individual projects of this program will lead to enhancement of our knowledge of primary, secondary and tertiary effectors in the signal transduction pathway(s) under study. Such information should prove important in understanding the molecular pathogenesis of a number of human malignancies and may well lead to the development of new diagnostic and therapeutic approaches to these diseases.